Publications by authors named "Mackenzie A C Sievert"
Background: Artemisinin partial resistance (ART-R) has spread throughout Southeast Asia and mutations in , the molecular marker of resistance, are widely reported in East Africa. Effective assays and robust phenotypes are crucial for monitoring populations for the emergence and spread of resistance. The recently developed extended Recovery Ring-stage Survival Assay used a qPCR-based readout to reduce the labor intensiveness for phenotyping of ART-R and improved correlation with the clinical phenotype of ART-R.
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- Artemisinin partial resistance (ART-R) has been detected in eastern Africa, prompting the need for ongoing monitoring of artemisinin susceptibility in malaria parasites.
- Traditional methods like the ring-stage survival assay (RSA) rely on microscopy, which is slow and subjective, while the new extended recovery ring-stage survival assay (eRRSA) uses qPCR for better efficiency and has proven effective on cultured clones.
- A study comparing both methods on 122 fresh isolates from Uganda showed strong correlations between results, with eRRSA offering a more scalable and effective approach to identifying resistance in malaria strains.
Article Synopsis
- Malaria causes over 550,000 deaths yearly, partly due to drug-resistant genes; many genes in the malaria genome remain functionally unknown, which hinders drug target identification.
- This study analyzes gene co-expression networks using various inference methods to improve functional annotations and validate genes, revealing high precision yet low recall in predicted annotations.
- The networks provide complementary insights into gene interactions, with unique edges, and offer ranked lists of gene interactions and predicted annotations for future research in malaria treatment.
Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the () and increased copies of (). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31).
View Article and Find Full Text PDFPiperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the () and increased copies of (). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31).
View Article and Find Full Text PDFCyclical regression covariates remove the major confounding effect of cyclical developmental gene expression with strain-specific drug response in the malaria parasite Plasmodium falciparum.
BMC Genomics
March 2022
Background: The cyclical nature of gene expression in the intraerythrocytic development cycle (IDC) of the malaria parasite, Plasmodium falciparum, confounds the accurate detection of specific transcriptional differences, e.g. as provoked by the development of drug resistance.
View Article and Find Full Text PDFBackground: Tracking and understanding artemisinin resistance is key for preventing global setbacks in malaria eradication efforts. The ring-stage survival assay (RSA) is the current gold standard for in vitro artemisinin resistance phenotyping. However, the RSA has several drawbacks: it is relatively low throughput, has high variance due to microscopy readout, and correlates poorly with the current benchmark for in vivo resistance, patient clearance half-life post-artemisinin treatment.
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